We are studying the enzymes that alter the tertiary and quaternary structure of DNA, the topoisomerases. The work focuses mainly on Escherichia coli DNA gyrase, an enzyme that introduces negative supercoils into circular DNA at the expense of ATP. We plan to purify large amounts of the enzyme to study the structure, activities, and mechanism of this enzyme essential for DNA replication. Mutants that overproduce or underproduce gyrase will be used to explore the physiological role of the enzyme. We have discovered an E. coli topoisomerase related to DNA gyrase that relaxes DNA and it will be characterized. finally we will search for new topoisomerases.